Approximately one million cells die every second in the course of normal tissue turnover in humans through apoptosis, a highly regulated process of programmed cell death (PCD). Cell death must swiftly and accurately be balanced with compensatory proliferation to maintain homeostasis and tissue integrity. Apoptosis, in addition to its role in cellular demise, has also been implicated in triggering homeostatic compensatory proliferation, whereby dying cells are thought to induce proliferation in their neighboring cells as a means to control cell number. The molecular components of apoptotic compensatory proliferation signaling and the underlying mechanism of compensatory proliferation remain unknown.
Promoting apoptosis has long been used as a main strategy for cancer drug discovery. Many cancer drugs induce apoptosis in cancer cells but frequently fail to eradicate solid tumors. The failure to eradicate particularly large tumors may be in large part due to this compensatory proliferation signaling mechanism. Understanding these natural mechanisms of compensatory proliferation has a profound therapeutic implication for cancer.